A successful drug development program requires a complete understanding of the clinical pharmacology of the agents being evaluated. The Clinical Pharmacology Research Core (CPRC) has as its primary interest the use of pharmacokinetic and pharmacodynamic concepts in the development of novel anticancer agents. The CPRC is directly responsible for the pharmacokinetic/pharmacodynamic analysis of numerous Phase I and II clinical trials conducted within the NCI. In addition, the CPRC provides direct pharmacokinetic support for many studies performed elsewhere in the extramural community. Within the section, we utilize compartmental and noncompartmental approaches to define the disposition of agents. Also, we are often required to characterize the plasma protein binding properties and metabolism of new agents through in vitro techniques. Several of our clinical trials have used adaptive control with a feedback mechanism to target particular plasma concentrations (e.g., suramin, CAI). The drugs with which the CPRC has had its greatest experience include: suramin, phenylacetate, phenylbutyrate, TNP-470, PMEA, AZT, PSC 833, CAI, DAB486IL2, IgG-RFB4-SMPT-dgA CD22, IgG-HD37-SMPT-dgA CD19, ormaplatin, UCN-01, flavopiridol, thalidomide, 9AC, intraperitoneal cisplatin, intraperitoneal carboplatin, docetaxel, and paclitaxel. Currently, we are characterizing the interaction between ketoconazole and docetaxel and understand the pharmacokinetics of MS275, perifosine and depsipeptide. We are currently condicting Phase I trials of CC5013 and 2ME, both angiogenesis inhibitors.